Knowledge about the structure, function and cellular makeup of the temporomandibular joint (TMJ) is critical in order to understand both the normal and pathological biology of this joint. Additionally, the role of the mandibular condyle in growth and development of the craniofacial complex must be elucidated in order to better treat dental malocclusions and other facial deformities. For these reasons we have embarked on a cellular and molecular study of the tissues comprising the TMJ. The goals of this proposal are to 1) isolate and characterize cells from the TMJ meniscus, the condylar articular surface and the condylar growth center, 2) devise a separation technique for the partitioning of these cells into specific phenotypic sub-populations, 3) define the effects of growth factors on the modulation of the cell phenotypes and 4) test the hypothesis that some of the cells in the TMJ are autocrine regulatory cells. This work has clinical significance because of the fact that temporomandibular joint disorders are the most common facial pain condition seen by medical and dental providers. These joint disorders represent a cluster of diseases of the masticatory apparatus which range from neuromuscular to rheumatoid disorders. Knowledge of the natural history, course, and causative agents of temporomandibular joint disorders is limited. Previous investigations into the cellular, biochemical, and molecular structure of the tissues comprising the TMJ are few in number and have failed to address the regulatory and reparative processes which occur within this joint. This proposal will attempt to delineate some of the biochemical and developmental processes in the TMJ by using sophisticated cell separation, biochemical and molecular biological techniques. The cell separation techniques will utilize countercurrent centrifugal elutriation, whereby cells can be separated and collected on the basis of size. Biochemical parameters which will be studied include all aspects of matrix synthesis, cell proliferation and differentiation and their regulation by known regulatory factors. Molecular techniques will be used to identify points of regulation (i.e. transcriptional vs. translational) for the regulatory factors. Finally, using both recombinant DNA technology and newly developed assays for the growth factors, transforming growth factor beta1 and basic fibroblast growth factor, we will determine if cells from the TMJ meniscus and mandibular condyle participate in paracrine and/or autocrine regulatory pathways.